PROJECT SUMMARY Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting up to 6 million Americans. The incidence of AF has stabilized over the last decade, and despite continued emphasis on optimizing treatment strategies for AF, their outcomes have largely not improved. These concerning findings indicate that the epidemic of AF persists and its burden is unabated in recent years. We hypothesize that the failure to control the AF epidemic is related to an inadequate understanding of co-existing conditions and the lack of knowledge on the impact of rurality and neighborhood characteristics on outcomes in AF. Indeed, most hospitalizations and deaths in AF patients are attributed to non-cardiovascular causes, suggesting that comorbid conditions play a significant role in outcomes. Functional status may also fundamentally impact outcomes and healthcare utilization in elderly patients with AF, and as such was highlighted as a key research opportunity in AF, yet is seldom available in AF cohorts. Finally, the communities in which people live affect the healthcare they receive and their overall health, and notably, rural populations experience a disproportionate burden of deaths due to heart disease. Thus, the central goal of our application is to define the impact of comorbidities, activities of daily living, rurality, and characteristics of the area in which the patient lives, on non-fatal and fatal outcomes (recurrence of AF, progression to permanent AF, ischemic stroke and transient ischemic attack, heart failure, dementia, healthcare utilization including hospitalizations, emergency department visits, and outpatient visits, and all-cause and cardiovascular death) in AF. We will respond to the urgent need to study the comorbidity burden in these elderly patients, a step that is essential to inform practice guidelines with clinically applicable performance measures, and will offer a unique opportunity to study the impact of rurality and neighborhood characteristics on outcomes in AF, which is not feasible using data from clinical trials, registries, claims, or the electronic medical record alone. The impact of these studies will be high as they will fill an important gap in our understanding of AF by providing data on the most critical factors associated with outcomes. The proposed research makes an efficient use of rich data available through the Rochester Epidemiology Project (R01 AG034676), a unique research infrastructure which captures the complete health care experience of patients living in a geographically defined population. The knowledge gained will provide new information of critical clinical relevance vital to design more effective interventions to manage AF and improve its outcomes.